Non-insulin dependent diabetes mellitus (NIDDM) affects approximately 7% of the United States population, with certain population group being at increased risk of developing the disease. NIDDM is preceded by a phase of impaired glucose tolerance (IGT) and consequently individuals with IGT are at increased risk of future NIDDM. In addition to subjects with IGT, women with a history of gestational diabetes mellitus (GDM) represent a group at high risk of subsequent NIDDM. The primary specific aim of the present proposal is to determine whether subjects with IGT or newly diagnosed NIDDM can have the progression of their glucose intolerance slowed or even reversed. A second aim of the study is to determine the importance of factors such as insulin resistance, insulin secretion and body fat distribution in predicting individuals who are likely to respond to an intervention aimed at slowing or reversing the progression to hyperglycemia. To address these issues, we propose to study 2 populations at increased risk of developing NIDDM. We will recruit 100 Asian-Americans and 100 women with a history of GDM as part of a multicenter national study. Newly diagnosed NIDDM subjects (with a fasting plasma glucose < 140 mg/dl), identified during the screening program, will also be studied. Subjects from each population will be randomized into 4 groups: a control group, a group undertaking diet and exercise modifications, a group receiving medication (glipizide), and a group receiving diet and exercise modification and medication. Subjects will undergo these interventions for a minimum 4 year period and during this time will have sequential measurements of glucose tolerance performed. This randomization scheme allows for factorial design and analysis. In addition, measurements of body fat distribution, insulin sensitivity, insulin secretion, lipid measurements, resting metabolic rate, maximal oxygen uptake, and quality of life will be made. The data obtained from this study will answer whether the above intervention strategies in subjects at high risk of developing NIDDM and/or in subjects with recently diagnosed NIDDM, can slow or reverse the deterioration in glucose metabolism that is commonly seen in these individuals. The results of this study will have implications for future public health strategies in the United States and world-wide.